This invention relates to vascular repair devices, and in particular intravascular stents, which are adapted to be implanted into a patient's body lumen, such as a blood vessel or coronary artery, to maintain the patency thereof. Stents are particularly useful in the treatment of atherosclerotic stenosis in arteries and blood vessels. More particularly, the invention concerns apparatus and methods of manufacturing tubing for the subsequent manufacture into drug-eluting stents, utilizing the process of metal injection molding (MIM) applied to biocompatible metals and metal alloys, ceramics, and ceramic-metal composite materials. These devices may have longitudinal/circumferential channels and/or depots directly molded into the tubing thereof to enable such devices to act as functional drug delivery vehicles having adequate drug reservoir capabilities.
Intravascular interventional devices such as stents are typically implanted within a vessel in a contracted state, and expanded when in place in the vessel in order to maintain the patency of the vessel to allow fluid flow through the vessel. Stents have a support structure such as a metallic structure to provide the strength required to maintain the patency of the vessel in which it is to be implanted, and are typically provided with an exterior surface coating to provide a biocompatible and/or hemocompatible surface. Since it is often useful to provide localized therapeutic pharmacological treatment of a blood vessel at the location being treated with the stent, it is also desirable to provide intravascular interventional devices such as stents with a biocompatible and/or hemocompatible surface coating of a polymeric material with the capability of being loaded with therapeutic agents, to function together with the intravascular devices for placement and release of the therapeutic drugs at a specific intravascular site.
Drug-eluting stent devices have shown great promise in treating coronary artery disease, specifically in terms of reopening and restoring blood flow in arteries stenosed by atherosclerosis. Restenosis rates after using drug-eluting stents during percutaneous intervention are significantly lower compared to bare metal stenting and balloon angioplasty. Restenosis is the normal reaction of the human body to a foreign body being implanted in one of the coronary, carotid, or peripheral arteries. The coating of bare metal stents with an anti-cancer drug is the current approach being considered in order to decrease or eliminate restenosis. However, current design and fabrication methods for drug-eluting stent devices are not optimal. Accordingly, various limitations exist with respect to such current design and fabrication methods for drug-eluting stents.
One significant limitation, for example, is that current designs for drug-eluting stents fail to provide for uniform drug distribution in the artery. Since uniformity is dictated by metal stent skeletal structure, increasing uniformity by increasing the metal stent surface area makes the stent stiff and compromises flexibility and deliverability. Additionally, current device designs incorporate expandable ring elements and connectors, which are then coated using a polymer plus drug coating or loaded with microreservoirs of drug. The expandable nature of the rings limits the extent of uniformity in coverage and drug distribution that can be achieved. Further limitations include the mixture of the drug in a polymer and/or solvent solution which is then spray coated on the entire stent surface with a primer, drug, and topcoat layers being used to control release kinetics. This approach tends to cause cracking in the drug-coating layer, since the layer also undergoes stretching during stent expansion, and resultant considerable washout of the drug into the blood stream, and only a fraction gets into the tissue/artery. Further, the amount of the drug that can be loaded on the stent is limited by mechanical properties of the coating, since the higher drug content in the polymer makes the coating more brittle and causes cracking thereto. Therefore, loading a higher drug dose requires coating with more polymer on the device. Other limitations in current fabrication methods of drug-eluting stents include the necessity of several coating steps along the length of the stent which is time consuming. Special equipment for crimping the drug-eluting stent on the balloon and to securely attach the stent on the balloon is also needed in accordance with current fabrication methods in order to prevent damage to the coating. As conventional spray coating is capable of programming only one drug release rate kinetics, variation of drug dosing and release kinetics along the length of the stent is not possible using the current coating process.
Several challenges face the major medical device manufacturing companies in regard to implementing a drug-eluting stent into the marketplace. A common method of applying an anti-cancer drug is to first apply a polymer primer layer to the bare metal stent, dissolve the drug into a suitable polymer using a suitable solvent, spray the drug-polymer mixture onto the primer layer, and then apply a polymer topcoat. One particular challenge facing medical device manufacturers is reducing the usage of such polymers. Medical device manufacturing companies are also faced with the challenge of making drug-eluting stents that have adequate drug storage capability. The creation of channels and/or depots into tubing using laser machining is one approach that has been considered to resolve this issue. However, it has been found that laser machining requires more control (i.e., consistency) in order to be a reliable and controlled manufacturing process. For example, in forming depots using laser machining, the depth thereof is not precisely repeatable from one depot to the next. Further, studies have shown that the use of laser machining in creating channels and/or depots into tubing is not a cost effective way to manufacture high volumes of components with intricate geometric shapes and designs at a competitive price.
What has been needed and heretofore unavailable in the art is a method of manufacturing tubing for the subsequent manufacture into drug-eluting stents that would increase the reservoir capacity of the stent by incorporating longitudinal and/or circumferential channels and geometrically-shaped depots into the abluminal surface of the tubing. Thus, it would be desirable to have a drug-eluting stent that is optimally designed to have increased drug storage capability, which improves the reproducibility of drug storage features currently being manufactured by the process of laser machining, hence eliminating the need for post laser machining of such channels and/or depots. The present invention meets these and other needs.